- Regioselective Electrochemical Cyclobutanol Ring Expansion to 1-Tetralones
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A mild electrochemical method for the regioselective preparation of 1-tetralones under environmentally friendly conditions from readily available cyclobutanols was developed. A series of aromatic- and heteroaromatic-fused 1-tetralones was accessed through ring expansion of the functionalized cyclobutanols via electrochemical generation of alkoxy radicals and intramolecular cyclization.
- Petti, Alessia,Natho, Philipp,Lam, Kevin,Parsons, Philip J.
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p. 854 - 858
(2021/01/12)
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- HISTONE ACETYLTRANSFERASE (HAT) INHIBITOR AND USE THEREOF
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The present invention relates to a histone acetyltransferase (HAT) inhibitor. Provided are a compound represented by general formula I, a pharmaceutically acceptable salt, a stereoisomer, an enantiomer, a diastereomer, an atropisomer, a racemate, a polymorph, a solvate or an isotope-labeled compound (including deuterium substitution) thereof, a preparation method therefor, a pharmaceutical composition comprising the same, and use thereof in the treatment of various HAT-related diseases or conditions.
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Paragraph 0482-0484
(2021/02/25)
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- Decarboxylative Intramolecular Arene Alkylation Using N-(Acyloxy)phthalimides, an Organic Photocatalyst, and Visible Light
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An intramolecular arene alkylation reaction has been developed using the organic photocatalyst 4CzIPN, visible light, and N-(acyloxy)phthalimides as radical precursors. Reaction conditions were optimized via high-throughput experimentation, and electron-rich and electron-deficient arenes and heteroarenes are viable reaction substrates. This reaction enables access to a diverse set of fused, partially saturated cores which are of high interest in synthetic and medicinal chemistry.
- Sherwood, Trevor C.,Xiao, Hai-Yun,Bhaskar, Roshan G.,Simmons, Eric M.,Zaretsky, Serge,Rauch, Martin P.,Knowles, Robert R.,Dhar, T. G. Murali
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p. 8360 - 8379
(2019/09/03)
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- Synthesis of Benzannulated Medium-ring Lactams via a Tandem Oxidative Dearomatization-Ring Expansion Reaction
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Medium-ring natural products exhibit diverse biological activities but such scaffolds are underrepresented in probe and drug discovery efforts due to the limitations of classical macrocyclization reactions. We report herein a tandem oxidative dearomatization-ring-expanding rearomatization (ODRE) reaction that generates benzannulated medium-ring lactams directly from simple bicyclic substrates. The reaction accommodates diverse aryl substrates (haloarenes, aryl ethers, aryl amides, heterocycles) and strategic incorporation of a bridgehead alcohol generates a versatile ketone moiety in the products amenable to downstream modifications. Cheminformatic analysis indicates that these medium rings access regions of chemical space that overlap with related natural products and are distinct from synthetic drugs, setting the stage for their use in discovery screening against novel biological targets.
- Guney, Tezcan,Wenderski, Todd A.,Boudreau, Matthew W.,Tan, Derek S.
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p. 13150 - 13157
(2018/09/10)
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- KDM4 INHIBITORS
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The present disclosure relates generally to compounds and methods for inhibiting the enzymatic activity of lysine demethylase 4 (KDM4) and treating cancer. Provided herein are substituted pyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibiting lysine demethylase 4. Furthermore, the subject compounds and compositions are useful for the treatment of breast cancer and the like.
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Paragraph 00136
(2018/10/25)
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- Acid-promoted furan annulation and aromatization: An access to benzo[b]furan derivatives
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An unprecedented PTSA-promoted furan annulation and aromatization in one pot has been developed. This process offers a simple and efficient synthetic route for the construction of various highly substituted benzo[b]furan derivatives, which are widely used not only in drug active molecules but also organic semiconductor and organic light-emitting devices. The preliminary mechanism study indicated this transformation proceeded sequentially via furan annulation and aromatization.
- Ao, Jun,Liu, Yidong,Jia, Shiqi,Xue, Lu,Li, Dongmei,Tan, Yu,Qin, Wenling,Yan, Hailong
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supporting information
p. 433 - 440
(2018/01/03)
-
- Method for synthesizing tetralone compound
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The invention belongs to the technical field of organic compound synthesis, provides a method for synthesizing a tetralone compound, and aims at solving the problems that in an exiting tetralone compound synthesizing method, an expensive transition metal catalyst, such as a palladium catalyst, is needed, and a large quantity of oxidizing agent is needed during a reaction. Aryl is used for replacing cyclobutanol to serve as an initiator, under the action of a catalyst, an oxidizing agent and an additive, reacting is carried out for 1-8 h in a solvent at the temperature of 25 DEG C to 100 DEG C, and the tetralone compound is obtained. The method has the advantages that the reaction conditions are relatively moderate, cheap metal copper is adopted as the catalyst, ligand participation is not needed, and operation is easy, convenient and feasible.
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-
Paragraph 0029; 0030
(2016/10/07)
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- Discovery of Potent and Selective Agonists of δ Opioid Receptor by Revisiting the "message-Address" Concept
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The classic "message-address" concept was proposed to address the binding of endogenous peptides to the opioid receptors and was later successfully applied in the discovery of the first nonpeptide δ opioid receptor (DOR) antagonist naltrindole. By revisiting this concept, and based on the structure of tramadol, we designed a series of novel compounds that act as highly potent and selective agonists of DOR among which (-)-6j showed the highest affinity (Ki = 2.7 nM), best agonistic activity (EC50 = 2.6 nM), and DOR selectivity (more than 1000-fold over the other two subtype opioid receptors). Molecular docking studies suggest that the "message" part of (-)-6j interacts with residue Asp1283.32 and a neighboring water molecule, and the "address" part of (-)-6j packs with hydrophobic residues Leu3007.35, Val2816.55, and Trp2846.58, rendering DOR selectivity. The discovery of novel compound (-)-6j, and the obtained insights into DOR-agonist binding will help us design more potent and selective DOR agonists.
- Shen, Qing,Qian, Yuanyuan,Huang, Xiaoqin,Xu, Xuejun,Li, Wei,Liu, Jinggen,Fu, Wei
-
supporting information
p. 391 - 396
(2016/05/19)
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- SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
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Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
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Page/Page column 860
(2016/04/10)
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- A facile and regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion
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A regioselective synthesis of 1-tetralones via silver-catalyzed ring expansion is described. A variety of 1-tetralones are furnished under mild reaction conditions from tertiary cyclobutanols regardless of the electronic properties and steric hindrance of substituents, providing a new and practical method to access diverse 1-tetralone building blocks. Preliminary experimental and DFT studies revealed that a radical-mediated sequence of C-C bond cleavage/C-C bond formation is involved.
- Yu, Jiajia,Zhao, Huijun,Liang, Shuguang,Bao, Xiaoguang,Zhu, Chen
-
supporting information
p. 7924 - 7927
(2015/07/27)
-
- COMPOUNDS AND METHODS FOR TREATING HIV INFECTIONS
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The present invention is directed to novel nanomolar and picomolar inhibitors of HIV reverse transcriptase, pharmaceutical compositions therefrom and methods for inhibiting reverse transcriptase and treating HIV infections, especially included drug resistant strains of HIV-1 and HIV-2 and/or secondary disease states and/or conditions which occur as a consequence of HIV infection.
- -
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Paragraph 0447
(2015/04/21)
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- FUSED 1,4-DIHYDRODIOXIN DERIVATIVES AS INHIBITORS OF HEAT SHOCK TRANSCRIPTION FACTOR 1
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The present invention relates to compounds of formula I wherein A1, A2 R4 and Q are as defined herein. The compounds of the present invention are inhibitors of heat shock factor 1 (HSF1). In particular, the present invention relates to the use of these compounds as therapeutic agents for the treatment and/or prevention of proliferative diseases, such as cancer. The present invention also relates to processes for the preparation of these compounds, and to pharmaceutical compositions comprising them.
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-
Paragraph 0032
(2015/04/22)
-
- Modulators of methyl modifying enzymes, compositions and uses thereof
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.
- -
-
Page/Page column 170; 171
(2015/12/26)
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- Picomolar inhibitors of HIV-1 reverse transcriptase: Design and crystallography of naphthyl phenyl ethers
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Catechol diethers that incorporate a 6-cyano-1-naphthyl substituent have been explored as non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs). Promising compounds are reported that show midpicomolar activity against the wild-type virus and sub-20 nM activity against viral variants bearing Tyr181Cys and Lys103Asn mutations in HIV-RT. An X-ray crystal structure at 2.49 ? resolution is also reported for the key compound 6e with HIV-RT.
- Lee, Won-Gil,Frey, Kathleen M.,Gallardo-Macias, Ricardo,Spasov, Krasimir A.,Bollini, Mariela,Anderson, Karen S.,Jorgensen, William L.
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supporting information
p. 1259 - 1262
(2015/04/27)
-
- LYSOPHOSPHATIDIC ACID RECEPTOR ANTAGONISTS
-
Compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or diagnose diseases, disorders, or conditions associated with one or more of the lysophosphatidic acid receptors are provided.
- -
-
Paragraph 1156; 1157
(2014/07/23)
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- Potent BRAF kinase inhibitors based on 2,4,5-trisubstituted imidazole with naphthyl and benzothiophene 4-substituents
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The RAS-RAF-MEK-ERK pathway is hyperactivated in 30% of human cancers. BRAF is a serine-threonine kinase, belonging to this pathway that is mutated with high frequency in human melanoma and other cancers thus BRAF is an important therapeutic target in melanoma. We have designed inhibitors of BRAF based on 2,4,5-trisubstituted imidazoles with naphthyl and benzothiophene-4-substituents. Two compounds were discovered to be potent BRAF inhibitors: 1-(6-{2-[4-(2-dimethylamino-ethoxy)phenyl]-5-(pyridin-4-yl)-1H-imidazol-4-yl} benzo[b]thiophen-3-yl)-2,2,2-trifluoroethanol (1i) with BRAF IC50 = 190 nM and with cellular GI50 = 2100 nM, and 6-{2-[4-(2- dimethylamino-ethoxy)-phenyl]-5-pyridin-4-yl-3H-imidazol-4-yl}-naphthalen-1-ol (1q) with IC50 = 9 nM and GI50 = 220 nM.
- Niculescu-Duvaz, Dan,Niculescu-Duvaz, Ion,Suijkerbuijk, Bart M.J.M.,Ménard, Delphine,Zambon, Alfonso,Davies, Lawrence,Pons, Jean-Francois,Whittaker, Steven,Marais, Richard,Springer, Caroline J.
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p. 1284 - 1304
(2013/03/14)
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- MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
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Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein
- -
-
Paragraph 00344; 00345
(2013/06/05)
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- Copper-free asymmetric allylic alkylation of trisubstituted cyclic allyl bromides using grignard reagents
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AAA: The asymmetric allylic alkylation (AAA) of trisubstituted cyclic allyl bromides with Grignard reagents is catalytic (2 mol % of ligand) and regioselective (SN2'/SN2=91:9→100:0). The quaternary carbon centers are formed with good to high enantioselectivity (e.r.=81.5:19.5→96:4). Copyright
- Grassi, David,Alexakis, Alexandre
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supporting information
p. 13642 - 13646
(2014/01/06)
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- Isoselenazolones as catalysts for the activation of bromine: Bromolactonization of alkenoic acids and oxidation of alcohols
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Isoselenazolones were synthesized by a copper-catalyzed Se-N bond forming reaction between 2-halobenzamides and selenium powder. The catalytic activity of the various isoselenazolones was studied in the bromolactonization of pent-4-enoic acid. Isoselenazolone 9 was studied as a catalyst in several reactions: the bromolactonization of a series of alkenoic acids with bromine or N-bromosuccinimide (NBS) in the presence of potassium carbonate as base, the bromoesterification of a series of alkenes using NBS and a variety of carboxylic acids, and the oxidation of secondary alcohols to ketones using bromine as an oxidizing reagent. Mechanistic details of the isoselenazolone-catalyzed bromination reaction were revealed by 77Se NMR spectroscopic and ES-MS studies. The oxidative addition of bromine to the isoselenazolone gives the isoselenazolone(IV) dibromide, which could be responsible for the activation of bromine under the reaction conditions. Steric effects from an N-phenylethyl group on the amide of the isoselenazolone and electron-withdrawing fluoro substituents on the benzo fused-ring of the isoselenazolone appear to enhance the stability of the isoselenazolone as a catalyst for the bromination reaction.
- Balkrishna, Shah Jaimin,Prasad, Ch Durga,Panini, Piyush,Chopra, Deepak,Kumar, Sangit,Detty, Michael R.
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p. 9541 - 9552,12
(2012/12/12)
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- 4H-THIENO[3,2-C]CHROMENE-BASED INHIBITORS OF NOTUM PECTINACETYLESTERASE AND METHODS OF THEIR USE
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Compounds that may be used to inhibit Notum Pectinacetylesterase are described, as well as compositions comprising them, and methods of their use to treat diseases and disorders affecting bone.
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Page/Page column 21
(2012/12/13)
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- Design, synthesis, structure, and dehydrogenation reactivity of a water soluble o-iodoxybenzoic acid derivative bearing a trimethylammonium group
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5-Trimethylammonio-1, 3-dioxo-1, 3-dihydro-1λ5-benzo[d][1, 2]iodoxol-1-ol anion (AIBX 1a), an o-iodoxybenzoic acid (IBX) derivative having the trimethylammonium moiety on its phenyl ring, possesses very good solubility in water and distinct oxidative properties from IBX, which is demonstrated in the oxidation of various β-keto esters to the corresponding dehydrogenated products using water as cosolvent. The regeneration of AIBX 1a can be easily realized from the reaction mixture due to its good water solubility.2011 American Chemical Society.
- Cui, Li-Qian,Dong, Zhi-Lei,Liu, Kai,Zhang, Chi
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p. 6488 - 6491
(2012/02/02)
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- INHIBITORS OF HCV NS5A PROTEIN
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Provided herein are compounds, pharmaceutical compositions and combination therapies for treatment of hepatitis C.
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-
Page/Page column 32
(2012/01/05)
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- INHIBITORS OF HCV NS5A
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Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.
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-
Page/Page column 147
(2011/12/14)
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- INHIBITORS OF HCV NS5A
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Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.
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-
Page/Page column 147
(2010/06/20)
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- SPIROPYRROLIDINE BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE
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The present invention is directed to spiropyrrolidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease.
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-
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- OXAZOLIDINONE DERIVATIVES N-SUBSTITUTED BY A BICYCLIC RING, FOR USE AS ANTIBACTERIAL AGENTS
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Compounds of formula (I) and methods for their preparation are disclosed. Further disclosed are methods of making biologically active compounds of formula (I) as well as pharmaceutically acceptable compositions comprising compounds of formula (I). Compoun
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Page/Page column 87
(2010/02/08)
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- Selective κ-opioid agonists: Synthesis and structure-activity relationships of piperidines incorporating an oxo-containing acyl group
-
This study describes the synthesis and the structure-activity relationships (SARs) of the (S)-(-)-enantiomers of a novel class of 2- (aminomethyl)piperidine derivatives, using κ-opioid binding affinity and antinociceptive potency as the indices of biological activity. Compounds incorporating the 1-tetralon-6-ylacetyl residue (30 and 34-45) demonstrated an in vivo antinociceptive activity greater than predicted on the basis of their κ-binding affinities. In particular, (2S)-2-[(dimethylamino)methyl]- 1-[(5,6,7,8-tetrahydro-5-oxo-2-naphthyl)acetyl]piperidine (34) was found to have a potency similar to spiradoline in animal models of antinociception after subcutaneous administration, with ED50s of 0.47 and 0.73 μmol/kg in the mouse and in the rat abdominal constriction tests, respectively. Further in vivo studies in mice and/or rats revealed that compound 34, compared to other selective κ-agonists, has a reduced propensity to cause a number of κ-related side effects, including locomotor impairment/sedation and diuresis, at antinociceptive doses. For example, it has an ED50 of 26.5 μmol/kg sc in the rat rotarod model, exhibiting a ratio of locomotor impairment/sedation vs analgesia of 36. Possible reasons for this differential activity and its clinical consequence are discussed.
- Giardina,Clarke,Dondio,Petrone,Sbacchi,Vecchietti
-
p. 3482 - 3491
(2007/10/02)
-
- Certain [(1-imidazolyl)-lower-alkylene]-tetrahydronaphthalenecarboxylic acids or corresponding idan-carboxylic acids which are thromboxane A2
-
Benzocycloalkane derivatives of the formula (I) STR1 wherein: Z represents a methylene group or an ethylene group, either one of R1 and R2 represents --(CH2)m --COOR3 and the other represents STR2 whe
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